Infected versus sterile abdominal fluid collections in postoperative CT: a scoring system based on clinical and imaging findings.

PURPOSE: Characterization of intraabdominal fluid collections as postoperative complication is a challenging task. The aim was to develop and validate a new score to differentiate infected from sterile postoperative abdominal fluid collections and to compare it with a published score. MATERIALS AND METHODS: From May to November 2015, all patients with postoperative CT and C-reactive protein (CRP) 24 hours before CT-guided drainage were retrospectively included (Group A). HU, gas entrapment and wall enhancement of fluid collections were evaluated in the CT. All parameters were correlated with microbiology. To validate the score and to compare it with a published score, a second patient cohort was retrospectively recruited (Group B; January 2013-April 2015; December 2015-September 2016). RESULTS: In Group A (50 patients), univariate analysis confirmed that the four parameters were significantly associated with infected fluid collections. Based on binary logistic regression analysis, a score from 0 to 11 was developed (CRP

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population.

Obesity is one of the major risk factor for cardiovascular and metabolic diseases. A disproportional accumulation of fat at visceral (VAT) compared to subcutaneous sites (SAT) has been suspected as a key detrimental event. We used non-targeted metabolomics profiling to reveal metabolic pathways associated with higher VAT or SAT amount among subjects free of metabolic diseases to identify possible contributing metabolic pathways. The study population comprised 491 subjects [mean (standard deviation): age 44.6 yrs (13.0), body mass index 25.4 kg/m² (3.6), 60.1% females] without diabetes, hypertension, dyslipidemia, the metabolic syndrome or impaired renal function. We associated MRI-derived fat amounts with mass spectrometry-derived metabolites in plasma and urine using linear regression models adjusting for major confounders. We tested for sex-specific effects using interactions terms and performed sensitivity analyses for the influence of insulin resistance on the results. VAT and SAT were significantly associated with 155 (101 urine) and 49 (29 urine) metabolites, respectively, of which 45 (27 urine) were common to both. Major metabolic pathways were branched-chain amino acid metabolism (partially independent of insulin resistance), surrogate markers of oxidative stress and gut microbial diversity, and cortisol metabolism. We observed a novel positive association between VAT and plasma levels of the potential pharmacological agent piperine. Sex-specific effects were only a few, e.g. the female-specific association between VAT and O-methylascorbate. In brief, higher VAT was associated with an unfavorable metabolite profile in a sample of healthy, mostly non-obese individuals from the general population and only few sex-specific associations became apparent.

Holmium-166 Radioembolization in Hepatocellular Carcinoma: Feasibility and Safety of a New Treatment Option in Clinical Practice.

PURPOSE: To investigate clinical feasibility, technical success and toxicity of 166Ho-radioembolization (166Ho-RE) as new approach for treatment of hepatocellular carcinomas (HCC) and to assess postinterventional calculation of exact dosimetry through quantitative analysis of MR images. MATERIALS AND METHODS: From March 2017 to April 2018, nine patients suffering from HCC were treated with 166Ho-RE. To calculate mean doses on healthy liver/tumor tissue, MR was performed within the first day after treatment. For evaluation of hepatotoxicity and to rule out radioembolization-induced liver disease (REILD), the Model for End-Stage Liver Disease (MELD) Score, the Common Terminology Criteria for Adverse Events and specific laboratory parameters were used 1-day pre- and posttreatment and after 60 days. After 6 months, MR/CT follow-up was performed. RESULTS: In five patients the right liver lobe, in one patient the left liver lobe and in three patients both liver lobes were treated. Median administered activity was 3.7 GBq (range 1.7-5.9 GBq). Median dose on healthy liver tissue was 41 Gy (21-55 Gy) and on tumor tissue 112 Gy (61-172 Gy). Four patients suffered from mild postradioembolization syndrome. No significant differences in median MELD-Score were observed pre-, posttherapeutic and 60 days after 166Ho-RE. No deterioration of liver function and no indicators of REILD were observed. One patient showed a complete response, four a partial response, three a stable disease and one a progressive disease at the 6 months follow-up. CONCLUSION: 166Ho-RE seems to be a feasible and safe treatment option with no significant hepatotoxicity for treatment of HCC.

Hepatic Steatosis Is Associated With Adverse Molecular Signatures in Subjects Without Diabetes.

Background and Aims: Exaggerated hepatic triglyceride accumulation (i.e., hepatic steatosis) represents a strong risk factor for type 2 diabetes mellitus and cardiovascular disease. Despite the clear association of hepatic steatosis with impaired insulin signaling, the precise molecular mechanisms involved are still under debate. We combined data from several metabolomics techniques to gain a comprehensive picture of molecular alterations related to the presence of hepatic steatosis in a diabetes-free sample (N = 769) of the population-based Study of Health in Pomerania. Methods: Liver fat content (LFC) was assessed using MRI. Metabolome measurements of plasma and urine samples were done by mass spectrometry and nuclear magnetic resonance spectroscopy. Linear regression analyses were used to detect significant associations with either LFC or markers of hepatic damage. Possible mediations through insulin resistance, hypertriglyceridemia, and inflammation were tested. A predictive molecular signature of hepatic steatosis was established using regularized logistic regression. Results: The LFC-associated atherogenic lipid profile, tightly connected to shifts in the phospholipid content, and a prediabetic amino acid cluster were mediated by insulin resistance. Molecular surrogates of oxidative stress and multiple associations with urine metabolites (e.g., indicating altered cortisol metabolism or phase II detoxification products) were unaffected in mediation analyses. Incorporation of urine metabolites slightly improved classification of hepatic steatosis. Conclusions: Comprehensive metabolic profiling allowed us to reveal molecular patterns accompanying hepatic steatosis independent of the known hallmarks. Novel biomarkers from urine (e.g., cortisol glucuronide) are worthwhile for follow-up in patients suffering from more severe liver impairment compared with our merely healthy population-based sample.

Ductal Mucus Obstruction and Reduced Fluid Secretion Are Early Defects in Chronic Pancreatitis.

Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP), therefore we aimed to (i) investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii) to correlate the mucus phenotype with epithelial ion transport function. Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP) and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production. Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression. Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.

Navigator flip angle optimization for free-breathing T1-weighted hepatobiliary phase imaging with gadoxetic acid.

PURPOSE: To characterize and optimize the navigator-flip angle (FA), and the influence of imaging-FA on optimizing liver/lung contrast of the navigator profile, while avoiding visible navigator saturation artifacts, for hepatobiliary phase gadoxetic acid-enhanced MRI. MATERIALS AND METHODS: Ten volunteers; six men, four women; ages 37.1 ± 11.0 years underwent navigator-gated three-dimensional (3D) -spoiled-gradient-echo sequences in randomized combinations of imaging-FA (10°/30°) and navigator-FA (10-90°) before contrast and 20 min after injection of gadoxetic acid at 3 Tesla. The signal intensities of the liver and lung were measured from navigator profiles. Furthermore, the intensity of saturation artifacts for each navigator FA was quantified using measurements of relative contrast at the artifact location. RESULTS: For the postcontrast images, the optimal navigator FA was 90°. However, saturation artifacts were highly dependent on the imaging-FA and the presence of gadolinium contrast. A smaller imaging-FA of 10° led to greater saturation artifacts for both pre- and postcontrast, and saturation artifacts worsen with increasing navigator-FA. Using a higher imaging-FA of 30°, saturation artifacts are ignorable over the entire range of navigator-FA. CONCLUSION: For navigator-gated gadoxetic acid-enhanced hepatobiliary imaging, navigator-FA of 90° and imaging-FA of 30° provide an optimal balance with maximum navigator liver/lung contrast while avoiding visible imaging saturation artifacts.J. Magn. Reson. Imaging 2014;40:1129-1136. © 2013 Wiley Periodicals, Inc.

Characterization of the intestinal and hepatic uptake/efflux transport of the magnetic resonance imaging contrast agent gadolinium-ethoxylbenzyl-diethylenetriamine-pentaacetic acid.

OBJECTIVES: The objectives of the study were to measure the pharmacokinetics and liver enhancement of gadoxetate (gadolinium-ethoxylbenzyl-diethylenetriamine-pentaacetic acid [Gd-EOB-DTPA], Eovist, Primovist) after oral and intravenous administration in wild-type and (multidrug resistance-associated protein 2) Mrp2-deficient rats and to evaluate the in vitro transport of the contrast agent via intestinal and hepatic transporter proteins. MATERIALS AND METHODS: Gadolinium-ethoxylbenzyl-diethylenetriamine-pentaacetic acid-enhanced magnetic resonance imaging and pharmacokinetics of Gd-EOB-DTPA after intravenous and oral administration were evaluated in wild-type and Mrp2-deficient rats using T1-weighted magnetic resonance imaging and a validated liquid chromatography-mass spectrometry method, respectively. Cellular uptake of Gd-EOB-DTPA was measured in stably transfected human embrionic kidney 293-cells expressing oragnic anion-transporting polypeptide 1A2 or organic cation transporter 3 and Madin Darby canine kidney 2-cells expressing apical sodium dependent bile acid transporter. The affinity to MRP2 and multidrug resistance-associated protein 3 was measured using inside-out vesicles. RESULTS: In vitro, Gd-EOB-DTPA was demonstrated to be a substrate for OATP1A2 (mean [SD] of the Michaelis-Menten constant [K(m)], 1.0 [0.4] mmol/L; mean [SD] of the maximal uptake rate [V(max)], 101.3 [21.1] pmol/mg per minute), MRP2 (K(m), 1.0 [0.5] mmol/L; V(max), 86.8 [31.1] pmol/mg per minute), and multidrug resistance-associated protein 3 (K(m), 1.8 [0.3] mmol/L; V(max), 116 [15.9] pmol/mg per minute) but not for the apical sodium-dependent bile acid transporter and organic cation transporter 3. After the oral administration to the wild-type animals, Gd-EOB-DTPA was considerably absorbed from the small intestine (bioavailability, approximately 17%) and predominately eliminated via feces after intravenous dosing (approximately 96%). In the Mrp2-deficient rats, oral bioavailability increased to approximately 21% and Gd-EOB-DTPA was exclusively excreted into urine. Magnetic resonance enhancement of the liver was significantly prolonged in the Mrp2-deficient rats compared with the wild-type rats (mean [SD] area under the curve0-90, 36.4 [8.5] vs 14.8 [10.3] arbitary units per minute; P = 0.003; time to maximum plasma concentration, 48.6 [23.8] vs 6.0 [3.1] minutes; P = 0.001). CONCLUSIONS: The nonmetabolized Gd-EOB-DTPA may have some potentials to be used as a probe-contrast agent to evaluate transporter-mediated mechanisms along the enterohepatic absorption route for drugs by functional visualization in vivo.

Selective microcoil embolization of arterial gastrointestinal bleeding in the acute situation: outcome, complications, and factors affecting treatment success.

OBJECTIVES: To evaluate microcoil embolization in the interventional treatment of acute upper and lower gastrointestinal bleeding. PATIENTS AND METHODS: Forty-four patients (29 men, 15 women) with active arterial gastrointestinal bleeding were treated with microcoil embolization. The analysis included technical/clinical success, morbidity, mortality, and intervention-related mortality. Age, sex, underlying malignant disease, number of embolizations, preinterventional and postinterventional hemoglobin levels, blood products administered peri-interventionally, amount of embolization material used, duration of fluoroscopy, and use of contrast medium were evaluated for possible effects on technical and clinical success. RESULTS: The primary technical success rate of microcoil embolization for acute gastrointestinal bleeding was 88.6% with a clinical success rate of 56.8%. Minor and major complications occurred in 13.6 and 18.2% of patients, respectively. Intervention-associated mortality, due to intestinal ischemia, accounted for 4.6% of the total 18.2% mortality rate. Patients with technically successful embolization had a statistically significant increase in hemoglobin (P<0.01) after the intervention and a decrease in need for packed red blood cells, (P<0.01), fresh frozen plasma (P<0.01), and coagulation products (P<0.01). A smaller postinterventional fresh frozen plasma requirement was associated with a better clinical outcome (P=0.02). CONCLUSION: Microcoil embolization of arterial gastrointestinal bleeding in the acute situation has a high-technical success rate. The number of transfusions required before and after the intervention has no significant effect on technical success. Postinterventional fresh frozen plasma demand negatively correlates with clinical success.

A fast and accurate automatic lung segmentation and volumetry method for MR data used in epidemiological studies.

In modern epidemiological population-based studies a huge amount of magnetic resonance imaging (MRI) data is analysed. This requires reliable automatic methods for organ extraction. In the current paper, we propose a fast and accurate automatic method for lung segmentation and volumetry. Our approach follows a "coarse-to-fine" segmentation strategy. First, we extract the lungs and trachea excluding the main pulmonary vessels. This step is executed very fast and allows for measuring the volume of both structures. Thereafter, we start a refinement procedure that consists of three main stages: trachea extraction, lung separation, and filling the cavities on the final lung masks. After the trachea extraction step the volumes of both lungs without the main vessels can be measured. The final segmentation step results in the volumes of the left and right lungs including the vessels. The method has been tested by processing MR datasets from ten healthy participants. We compare our results with manually produced masks and obtain high agreement between the expert reading and our method: the True Positive Volume Fraction is more than 95%. The proposed automatic approach is fast and accurate enough to be applied in clinical routine for processing of thousands of participants.

In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model.

BACKGROUND: Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability. METHODS: 6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA. RESULTS: MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm3+/-243 mm3) with MRI (mean 918 mm3+/-193 mm3) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm2+/-22.8 mm2 versus 32.6 mm2+/-22.6 mm2 (histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm3+/-56.7 mm3 after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals. CONCLUSIONS: This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.

Percutaneous biliary drainage in patients with nondilated intrahepatic bile ducts compared with patients with dilated intrahepatic bile ducts.

OBJECTIVE: The purpose of this article is to compare the technical success and guidance of percutaneous transhepatic biliary drainage (PTBD) in patients with nondilated and dilated bile duct systems using different techniques to supplement the conventional approach. MATERIALS AND METHODS: Between 2006 and 2008, 71 patients (mean age, 66.6 years) underwent PTBD with 97 interventions. According to sonographic evaluation of bile duct morphology, patients were divided into two groups: 50 patients with dilated and 21 patients with nondilated bile ducts. In a retrospective analysis, both groups were compared for technical success, fluoroscopy time, complications, and medical indications. The use of interventional guidance (deviations from the standard protocol) in patients with nondilated bile ducts was recorded. RESULTS: The technical success rate was 90% in patients with dilated bile ducts versus 81% in patients with nondilated ducts, with no significant difference (p = 0.36). The greater complexity of the intervention in patients with nondilated bile ducts resulted in longer fluoroscopy times (p = 0.04). Complication rates were not different between the two groups. The main indication for PTBD was relief of a compressed biliary system in patients with dilated ducts and postoperative management of complications or prevention of tumor-associated bile duct obstruction in patients with nondilated ducts. T-drainage, additional CT-guided puncture, and temporary gallbladder drainage were performed in 16 of 21 interventions for patients with nondilated bile ducts, resulting in a 100% success rate, versus a success rate of 60% in the five PTBDs of nondilated ducts performed in the conventional manner. CONCLUSION: T-drainage, additional CT-guided puncture, and temporary gallbladder drainage improve the technical success of PTBD when used in patients with nondilated bile ducts. With these measures, technical success and complication rates in patients with nondilated ducts are comparable to those for PTBD of dilated bile ducts.